Recently, public interest in Cannabis as medicine has been growing, based in no small part on the fact that Cannabis has long been considered to have medicinal properties, ranging from treatment of cramps, migraines, convulsions, appetite stimulation and attenuation of nausea and vomiting. In fact, a report issued by the National Academy of Sciences' Institute of Medicine indicated that the active components of Cannabis appear to be useful in treating pain, nausea, AIDS-related weight loss or “wasting”, muscle spasms in multiple sclerosis as well as other problems. Advocates of medical marijuana argue that it is also useful for glaucoma, Parkinson's disease, Huntington's disease, migraines, epilepsy and Alzheimer's disease.
Marijuana refers to varieties of Cannabis having a high content of Δ9-tetrahydrocannabinol (Δ9-THC), which is the psychoactive ingredient of marijuana whereas industrial hemp refers to varieties of the Cannabis plant that have a low content of Δ9-THC.
Furthermore, Δ9-THC is only one of a family of about 60 bi- and tri-cyclic compounds named cannabinoids. For example, Δ8-THC is a double bond isomer of Δ9-THC and is a minor constituent of most varieties of Cannabis (Hollister and Gillespie, 1972, Clin Pharmacol Ther 14: 353). The major chemical difference between the two compounds is that Δ9-THC is easily oxidized to cannabinol whereas Δ8-THC does not and is in fact very stable. Δ8-THC, for the most part, produces similar psychometric effects as does Δ9-THC, but is generally considered to be 50% less potent than Δ9-THC and has been shown in some cases to be 3-10 times less potent. Δ8-THC has also been shown to be more (200%) effective an anti-emetic than Δ9-THC and has been used as an anti-emetic in children, based on the belief that the side effects of Δ9-THC and Δ8-THC, such as anxiety and dysphoria, are more prevalent in adults than children (Abrahamov et al, 1995, Life Sciences 56: 2097-2102). On the other hand, CBD has no activity on its own when administered to humans. It is of note that CBD is typically about 2% (0.5-4%) dry weight of hemp chaff, Δ8-THC is approximately 0.2% (0.05-0.5%) dry weight and Δ9-THC is approximately 0.1% (0.05-0.3%).
Gaoni and Mechoulam (1966, Tetrahedron 22: 1481-1488) teach methods of converting CBD to, among other compounds, Δ8-THC and Δ9-THC comprising boiling a solution of CBD (3.0 g) in absolute ethanol (100 ml) containing 0.05% HCl for 18 hours. The solution was then poured into water and extracted with ether. The ether solution was washed with water, dried (Na2SO4) and evaporated. Δ8-THC and Δ9-THC were eluted from the resulting oil and separated by chromatography. In another experiment, CBD (3.14 g) was dissolved in benzene (100 ml) containing 2 mg/ml p-toluenesulphonic acid and boiled for two hours. The reaction mixture was poured into water and the upper layer was separated, washed with 5% NaHCO3, then with water, dried and evaporated. Elution with pentane-ether (95:5) gave an oily material which was subsequently distilled. Percentage yield of Δ8-THC (Δ1(6)-THC) was given as 64% of the crude material in this paper. The crude oil product, which showed only one spot by thin layer chromatography, was purified by vacuum distillation.
Gaoni and Mechoulam (1964, J Amer Chem Soc 86: 1646) also described a method for converting CBD to Δ9-THC comprising boiling a mixture of CBD in ethanol containing 0.05% hydrogen chloride for 2 hours. Percentage yield of Δ9-THC (Δ1-THC) was 2% (Mechoulam et al, 1972, J Amer Chem Soc 94: 6159-6165; Mechoulam and Gaoni, 1965, J Amer Chem Soc 87: 3273). Using boron trifluoride, the yield was 70% (Gaoni and Mechoulam, 1971, J Amer Chem Soc 93: 217-224) although purity was not given.
Clearly, as the cannabinoids are of potential medicinal value, improved methods of converting CBD to Δ9-THC or Δ8-THC are needed.